Upregulation of microRNA-22 contributes to myocardial ischemia-reperfusion injury by interfering with the mitochondrial function

Du, Jiankui; Cong, Binhai; Yu, Qing; Wang, He; Wang, Long; Wang, Chang-Nan; Tang, Xiaolu; Lu, Jianqiang; Zhu, Xiaoyan; Ni, Xin

doi:10.1016/j.freeradbiomed.2016.05.006

Cited by 87 publications

(89 citation statements)

References 55 publications

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“…In recent decades, the vital function of miRNAs in cardiovascular disease has been well characterized. Among them is miRNA‐22‐3p, which was shown to be enriched in strained muscle tissues and has been confirmed to be involved in various cardiovascular disorders through regulating inflammation, apoptosis, oxidative stress and autophagy . In our present study, we transfected cardiomyocytes with adenovirus containing siRNA to down‐regulate the miRNA‐22‐3p level to explore its effect on AMI.…”

Section: Discussionmentioning

confidence: 88%

LncRNA H19 ameliorates myocardial infarction‐induced myocardial injury and maladaptive cardiac remodelling by regulating KDM3A

Zhang

Jiang

Chen

et al. 2019

J Cellular Molecular Medi

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Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide, and novel therapeutic targets still need to be investigated to alleviate myocardial injury and the ensuing maladaptive cardiac remodelling. Accumulating studies have indicated that lncRNA H19 might exert a crucial regulatory effect on cardiovascular disease. In this study, we aimed to explore the biological function and molecular mechanism of H19 in MI. To investigate the biological functions of H19, miRNA‐22‐3p and KDM3A, gain‐ and loss‐of‐function experiments were performed. In addition, bioinformatics analysis, dual‐luciferase reporter assays, RNA immunoprecipitation (RIP) assays, RNA pull‐down assays, quantitative RT‐PCR and Western blot analyses as well as rescue experiments were conducted to reveal an underlying competitive endogenous RNA (ceRNA) mechanism. We found that H19 was significantly down‐regulated after MI. Functionally, enforced H19 expression dramatically reduced infarct size, improved cardiac performance and alleviated cardiac fibrosis by mitigating myocardial apoptosis and decreasing inflammation. However, H19 knockdown resulted in the opposite effects. Bioinformatics analysis and dual‐luciferase assays revealed that, mechanistically, miR‐22‐3p was a direct target of H19, which was also confirmed by RIP and RNA pull‐down assays in primary cardiomyocytes. In addition, bioinformatics analysis and dual‐luciferase reporter assays also demonstrated that miRNA‐22‐3p directly targeted the KDM3A gene. Moreover, subsequent rescue experiments further verified that H19 regulated the expression of KDM3A to ameliorate MI‐induced myocardial injury in a miR‐22‐3p‐dependent manner. The present study revealed the critical role of the lncRNAH19/miR‐22‐3p/KDM3A pathway in MI. These findings suggest that H19 may act as a potential biomarker and therapeutic target for MI.

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Section: Discussionmentioning

confidence: 88%

LncRNA H19 ameliorates myocardial infarction‐induced myocardial injury and maladaptive cardiac remodelling by regulating KDM3A

Zhang

Jiang

Chen

et al. 2019

J Cellular Molecular Medi

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“…In contrast, miR‐22 has detrimental effect on adult cardiomyocytes under hypoxia/oxygenation (H/R) condition. The elevation of miR‐22 induces oxidative damage in H9C2 cells under H/R stress by targeting mitochondrial oxidative stress protectors sirtuin‐1 (Sirt1) and peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC1α) . This indicates that narrowed perspective should be limited while investigating diverse role of miRNAs.…”

Section: Mirnas Regulate Mitochondrial Calcium Homeostasis Related Prmentioning

confidence: 99%

Effects of miRNAs on myocardial apoptosis by modulating mitochondria related proteins

Zhao

Ponnusamy

Dong

et al. 2017

Clin Exp Pharma Physio

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“…Downregulation of miR-320 can protect against myocardial I/R injury by inhibiting cardiomyocyte apoptosis and targeting insulin-like growth factor-1 (IGF-1) [9]. Upregulation of miR-22 can interfere with the mitochondrial function to aggravate I/R-induced mitochondrial damage [10]. Recently, miR-486 has been identified as a key regulator in the development of various cancers, including gastric cancer [11], cervical cancer [12] and prostate cancer [13].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-486 Alleviates Hypoxia-Induced Damage in H9c2 Cells by Targeting NDRG2 to Inactivate JNK/C-Jun and NF-κB Signaling Pathways

Zhang¹,

Zhang²,

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Acute myocardial infarction is a serious disease with high morbidity and mortality. microRNAs (miRNAs) have been proved to play an important role in modulating myocardial ischemia and reperfusion injury. Hence, in this study, we constructed H9c2 cell model to elucidate the roles of microRNA-486 (miR-486) in preventing hypoxia-induced damage in H9c2 cells. Methods: H9c2 cells were cultured in hypoxic incubator with 1% O₂ to simulate hypoxia and/or transfected with miR-486 mimic, scramble, anti-miR-486, si-N-myc downstream-regulated gene 2 (NDRG2) and their corresponding negative controls (NC). Effects of miR-486 and/or NDRG2 dysregulation on hypoxia-induced myocardial injury in H9c2 cells were investigated by evaluating cell viability, migration, invasion and apoptosis using Cell Counting Kit-8 (CCK-8), transwell assay, flow cytometry, respectively. The proteins expression and RNA expression were detected by western blot and quantitative real time polymerase chain reaction (qRT-PCR), respectively. Results: Hypoxia treatment induced damage in H9c2 cells by decreasing cell viability, migration and invasion and increasing cell apoptosis. Moreover, hypoxia inhibited the expression of miR-486 in H9c2 cells. Overexpression of miR-486 alleviated hypoxia-induced myocardial injury in H9c2 cells, while suppression of miR-486 further aggravated hypoxia-induced injury. Furthermore, NDRG2 expression was negatively regulated by miR-486, and NDRG2 was confirmed as a target of miR-486. Knockdown of NDRG2 alleviated the effects of miR-486 suppression on hypoxia-induced myocardial injury. Besides, knockdown of NDRG2 markedly inhibited the activation of c-Jun N-terminal kinase (JNK) /c-jun and nuclear factor κB (NF-κB) signaling pathways in hypoxia-induced H9c2 cells. Conclusion: Our findings indicate that miR-486 may alleviate hypoxia-induced myocardial injury possibly by targeting NDRG2 to inactivate JNK/c-jun and NF-κB signaling pathways. miR-486 may be a potential target for treating ischemic myocardial injury following acute myocardial infarction.

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Upregulation of microRNA-22 contributes to myocardial ischemia-reperfusion injury by interfering with the mitochondrial function

Cited by 87 publications

References 55 publications

LncRNA H19 ameliorates myocardial infarction‐induced myocardial injury and maladaptive cardiac remodelling by regulating KDM3A

LncRNA H19 ameliorates myocardial infarction‐induced myocardial injury and maladaptive cardiac remodelling by regulating KDM3A

Effects of miRNAs on myocardial apoptosis by modulating mitochondria related proteins

MicroRNA-486 Alleviates Hypoxia-Induced Damage in H9c2 Cells by Targeting NDRG2 to Inactivate JNK/C-Jun and NF-κB Signaling Pathways

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